Plot

Alice (Milla Jovovich) and the others on the Umbrella Corporation freighter Arcadia face an attack by a fleet of tiltrotors led by Alice’s former ally, Jill Valentine (Sienna Guillory), who is being mind controlled by Umbrella through a scarab device attached to her chest. Alice causes a tiltrotor to crash into Arcadia, resulting in an explosion that knocks her out and into the water. The fates of Chris Redfield, Claire Redfield and K-Mart are left ambiguous.

The story switches to a suburban housewife who appears to be Alice living with her husband Todd (Oded Fehr) and deaf daughter Becky (Aryana Engineer). Zombies attack, revealing the suburbia is actually Raccoon City during the contamination. Alice and Becky escape to the streets and are rescued by a student, Rain Ocampo (Michelle Rodriguez), who lets them ride in her car. As the three escape, they are broadsided by a truck, knocking Rain unconscious while Alice and Becky escape. Alice hides Becky, but is killed by a zombified Todd.

The original Alice awakens to see she’s been captured. Jill interrogates Alice, who unsuccessfully tries jogging her memory, and demands to know what happened to Chris, Claire, and K-Mart. During a power failure, Alice escapes her cell and the laser grid, finding herself on the Shibuya Square, just at the beginning of the Tokyo contamination. Fighting her way out, she returns into the facility, and encounters Ada Wong (Li Bingbing), one of Albert Wesker’s (Shawn Roberts) top agents. Ada explains that they no longer serve Umbrella and the power outage was staged by Wesker hacking into the facility’s computers. Wesker appears on a screen, revealing the Red Queen, who was reactivated after the contamination of The Hive, now controls Umbrella. Ada explains that the facility is underwater, located in Kamchatka, Russia, that served as a former Soviet outpost; as the Hive was designed in producing the T-virus, the facility was designed by Umbrella in manufacturing clones and created simulated outbreaks to show the effect of the T-virus, and thus selling it at high price around the world.

To infiltrate the facility from outside and help Alice and Ada escape, Wesker has organized a strike team, Leon S. Kennedy (Johann Urb), Barry Burton (Kevin Durand), and Luther West (Boris Kodjoe). Leon’s team plants explosives near the entrance of the facility, which will detonate in two hours and trap anybody still inside, to ensure the facility’s destruction. The group plans to meet with Alice and Ada in the Raccoon City suburbia. In a New York City simulation, Alice and Ada defeat two Axemen, prompting the Red Queen to send Jill after them next. Leon and his team enter a Moscow simulation, but are attacked by armed Las Plagas Undead.

Alice and Ada enter the suburban simulation, the rendezvous point, and discover Becky and the dead “suburban Alice”. Ada explains that Umbrella uses clones for virus outbreak simulations and troops; Becky, Todd, and Rain were clones as well. Despite this, Alice quickly becomes attached to Becky. Blocking their escape are Jill and Umbrella troops, consisting of clones of Alice’s deceased allies, an “evil” version of Rain, modified after the original, a former deceased Umbrella soldier and Alice’s ally, Carlos Olivera (Oded Fehr), and also James “One” Shade (Colin Salmon), leader of an Umbrella commando team that was sent in The Hive. The group demand their immediate surrender, which Alice complies with for Becky’s safety; however, Ada starts a shoot-out, allowing Alice to escape with Becky.

Alice and Becky run into the “good” Rain and head to the Moscow simulation, where they meet Leon’s team. The group escapes the Las Plagas Undead, and reach the elevator; however, an Uber-Licker captures Becky and kills “good” Rain by throwing her into a pillar, breaking her neck. Alice pursues the Uber-Licker, while the others fight off Jill’s group; Barry and One are casualties. Alice rescues Becky despite Leon’s discouragement. During their escape, they arrive at a cloning facility where Alice and Becky see copies of themselves. When Becky asks Alice if she really is her mother, Alice says “she is now”. The Uber-Licker follows them inside, as Alice drops grenades, and fires a grappling hook, escaping the explosion. The explosives at the entrance go off, flooding the place (killing Olivera and the remaining Umbrella soldiers) and propelling the elevator upwards with Leon and Luther. Alice and Becky also survive, having used the ventilation system.

The group awaits pickup but is ambushed by a commandeered Soviet submarine, from which Jill, the “evil” Rain, and a captured Ada emerge. With new orders to kill Alice, Jill attacks. Rain injects herself with a Plagas parasite to gain superhuman strength and healing; she knocks out Ada and fights Leon and Luther. Alice manages to destroy the scarab device on Jill’s chest, returning her to normal, though, unlike Claire, she retains her memory. Rain kills Luther with a blow to the chest, and knocks Leon out; Alice, realizing they can’t kill Rain, shoots at her footing. Rain falls in the water, and vows to get Alice but is dragged under by zombies. Alice collapses from her injuries, but later awakes in a helicopter with the others.

Alice, Ada, Becky, Leon, and Jill travel to Wesker’s headquarters, the heavily barricaded and fortified White House, staffed by S.T.A.R.S. and the remainder of the U.S Military. Alice meets Wesker in the heavily-barricaded Oval Office, where he injects her with the T-virus, returning her superhuman abilities; as only Alice successfully bonded with it, she is the ultimate weapon. On the roof, Wesker explains the Red Queen is trying to wipe out humanity, and all of the remaining uninfected are in the base; it is humanity’s last stand. A pull-away shows the military defending the White House alongside the remaining U.S. Armed Forces against enormous hordes of T-virus abominations, including ones that fly.